literature

HIV mutation literature information.

Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance.

PMID: 19358668 2009 The Journal of infectious diseases

Abstract: Although thymidine analogue mutations had no effect on zidovudine sensitivity, the addition of Q151M together with K65R or M184V was sufficient for high-level resistance to both lamivudine and zidovudine in HIV-2, and the combination of K65R, Q151M, and M184V conferred classwide NRTI resistance.

Result: As a result, the HIV-2ROD mutant that contained K65R, Q151M, and M184V showed >=40-fold resistance to AZT, ddI, 3TC, and FTC; >10-fold resistance to ABC; and 4-5-fold resistance to d4T and PMPA.

Result: Finally, in the HIV-2ROD mutant that contained K65R, Q151M

The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy.

PMID: 19417582 2009 AIDS (London, England)

Abstract: Emergence of the K65R and K70E mutations was associated with CD4 cell count of less than 100 cells/microl (odds ratio 6.1) and inversely with the use of zidovudine (odds ratio 0.18).

Abstract: Twenty-three percent of patients acquired the K70E or K65R mutations associated with tenofovir resistance; 17% of the patients had pan-nucleoside resistance that corresponded to K65R or K70E and additional resistance mutations, most commonly the 151 complex.

Discussion: Additionally, we found the highest levels of resistance, as defined by at least three TAMs, K65R or 70E, or pan-nucleoside resistance, among those with CD4 cell count less than 100 cells/mul.

Effectiveness of antiretroviral therapy and development of drug resistance in HIV-1 infected patients in Mombasa, Kenya.

PMID: 19531211 2009 AIDS research and therapy

Abstract: The 3TC mutation M184V and the NNRTI mutation K103N were most frequent but also the multi-drug resistance Q151M and the broad NRTI cross-resistance K65R were observed.

Result: In one patient the multi-drug resistant Q151M mutation was seen and two patients carried virus with a K65R mutation, all three combined with V184M (Table S2; Additional File 2).

Discussion: However, the selection of K65R under a d4T containing regimen seems to be more common among non-B subtypes as observed by others.

Comparative analysis of in vitro processivity of HIV-1 reverse transcriptases containing mutations 65R, 74V, 184V and 65R+74V.

PMID: 19555722 2009 Antiviral research

Introduction: Although each are clinically important, K65R and L74V rarely occur on the same virus genome (Winters et al., 1997), and Stanford HIV drug resistance database (web site: http://hivdb.stanford.edu) confirm this rarity.

Introduction: Among 23 patients who received 1-2 years of 2',3'-dideoxyinosine (ddI) therapy, only one showed the presence of K65R and L74V on the same genome.

Introduction: Analysis of clinical data on the risks and incidence of K65R and L74V mutations on virologic responses have revealed that if suboptimal HAART is used, infected persons with K65R experienced significantly higher rates of virologic suppression than did those with L74V mutation.

Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure.

PMID: 19563238 2009 AIDS research and human retroviruses

Abstract: At the last time point analyzed, 4/14 subjects had wild-type HIV, while 10/14 subjects had HIV with either thymidine analogue mutations (TAMS) alone (3/10), TAMS + M184V (4/10), M184V only (1/10), or K65R/K (2/10).

Abstract: These data suggest that TAMs selection is a preferred resistance route of this combination, with zidovudine modulating the resistance pathway against selection for K65R.

Differences in resistance mutations among HIV-1 non-subtype B infections: a systematic review of evidence (1996-2008).

PMID: 19566959 2009 Journal of the International AIDS Society

Abstract: The main differences are reflected in the discoveries that: (i) the non-nucleoside reverse transcriptase inhibitor resistance mutation, V106M, has been seen in subtype C and CRF01_AE, but not in subtype B, (ii) the protease inhibitor mutations L89I/V have been reported in C, F and G subtypes, but not in B, (iii) a nelfinavir selected non-D30N containing pathway predominated in CRF01_AE and CRF02_AG, while the emergence of D30N is favoured in subtypes B and D, (iv) studies on thymidine analog-treated subtype C infections from South Africa, Botswana and Malawi have reported a higher frequency of the K65R resistance mutation than that typically seen with subtype B.Additionally, some substitutions that seem to impact non-B viruses differentially a

HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme.

PMID: 19578237 2009 Antiviral therapy

Abstract: In total, 10 (9%) patients had the K65R mutation.

Abstract: Three patients had one significant reverse transcriptase mutation: K65R, Y181C and G190A.

Discussion: Doualla-Bell noted that d4T also selected for K65R in subtype C virus in Botswana, and that the mutation developed within 3 months of tenofovir therapy, unlike in subtype B where the K65R tends to emerge slowly in a small proportion of individuals on tenofovir.

Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania.

PMID: 19583845 2009 BMC infectious diseases

Table: K65R

Anti-human immunodeficiency virus activity, cross-resistance, cytotoxicity, and intracellular pharmacology of the 3'-azido-2',3'-dideoxypurine nucleosides.

PMID: 19596885 2009 Antimicrobial agents and chemotherapy

Abstract: Importantly, both 3'-azido-ddA and 3'-azido-ddG retain activity against viruses containing K65R, L74V, or M184V (IC50 change of <2.0-fold) and against those containing three or more thymidine analog mutations (IC50 change of <3.5-fold).

Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure.

PMID: 19626612 2009 Journal of medical virology

Abstract: In this study, non-subtype B viruses possessed the K65R mutation at higher incidence than subtype B viruses.

Abstract: None of the eight viruses with K65R harbored thymidine analogue mutations.

Abstract: Recently, in vitro studies have shown that K65R is selected in tissue culture more rapidly with subtype C than subtype B viruses.

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